The packaging of chromosome, a phase separation perspective

Seminar:

Yiqin Gao

Spatial organization of DNA into chromosomes, which can be characterized by cell-specific interactions between local or long range segments, is thought to contribute to controlling and regulating essential nuclear functions in cells, but is only partially understood. In this talk, we describe a multi-scale approach that has been applied to understand this problem. Using molecular dynamics simulations we showed that DNA structure can be significantly affected by epigenetic modifications such as DNA methylation, the distribution of which shows disease (e.g., cancer)-dependent scale-invariant behavior in various biological samples. We then utilized Hi-C data to construct models for autosomes of different types of human cells and show that the epigenetic markers are strongly related to the 3-D chromosome structure. The high-order structure of chromosome is thus thought to be strongly affected by the DNA sequence. The DNA sequence is characterize by multi-scale clustering of dinucleotides and the human genome can be roughly viewed as a co-polymer. We try to make a connection of such a property of genome to the higher-order chromosome structure formation, including topologically associated domains (TADs) and compartments. Finally, we will discuss the tissue-specific organization of the chromosome structure in differentiation, development, and disease, in which segregation/intermingling of DNA segments of different properties characterized by CGI (CpG islands) distribution and transcription factor binding play important roles.